Oropharyngeal Microbiota Research Articles

488. Association between the Respiratory Microbiota and Response to Antibiotic Therapy in Children with Macrolide-resistant Mycoplasma pneumoniae Pneumonia

Abstract Background Along with the overuse of macrolides as the empirical treatment for M. pneumoniae infection, macrolide-resistant M. pneumoniae (MRMP) emerged up to 90 prevalence rate in Asian countries. We investigated whether respiratory microbiota at the beginning of hospitalization was associated with disease severity and response to antibiotic treatment in children with MRMP pneumonia. Methods Prospectively enrolled children aged < 18 years with community-acquired pneumonia caused by MRMP from 2017/4-2020/3 at Linkou Chang Gung Memorial Hospital. Oropharyngeal samplings were collected within 48 hours after admission. Total 66 children were included: 23 had not received macrolide or gave response to macrolide (defined as without effective treatment group); 43 needed doxycycline treatment (defined as doxycycline treatment group). Compared the oropharyngeal microbiota between groups using the 16S-rRNA-based sequencing. Patients who were administered antibiotics other than augmentin or Azithromax were excluded. The difference in microbial composition will be examined using microbial community analysis. Statistically significant species for each group were evaluated by the linear discriminant analysis of effect size analysis to identify differentially abundant biomarkers, comparing disease severity scores, CRP and febrile days lasting. Scheme of sample collection and analyses Augmentin with or without Azithromax was the most common antimicrobial agent used. If fever persisted under the impression of suspected MRMP infection, doxycycline was used following three days of Azithromax usage. Scheme of sample collection and analyses Correlation between microbiome and clinical feature. Results Doxycycline treatment group had longer duration of total febrile days (p< 0.001) and total hospitalization days (p=0.002). Without effective treatment group had higher microbial richness, different overall community composition (p< 0.01). The lowest respiratory alpha diversity had prolonged febrile days (p=0.032). Without effective treatment group had more abundant spices or genera. Classification of samples to detect patients with effective treatment or not based on these selected microbiota genera features achieved the ROC curve of 0.86. From the list of most relatively abundant species in MRMP patient without doxycycline, Fusobacterium periodonticum most negatively correlated with total febrile days and severity score. Clinical characteristics of patients enrolled in this study Data were shown as n (%) or mean ± standard deviation. N/A, not applicable. Taxonomic assignment of the all throat swab samples. Fraction of predominant microbiota with a relative abundance of at least 2% at the order level (A) and genus level (B) in all sample. Higher respiratory microbial diversity is associated with MRMP patients without effective treatment than MRMP patients who needed doxycycline treatment Microbial richness base on the different alpha-diversity index in MRMP patients without effective treatment (blue); MRMP patients with doxycycline treatment (red). (A)(B)The box represented the interquartile range (IQR, and the midline represented the median. Tukey’s honest significance test of ANOVA, p<0.05.) (C)Kaplan-Meier (KM) plot of febrile time by respiratory diversity. (D)Principal coordinates analysis (PCoA) for MRMP patients without effective treatment (blue), MRMP patients with doxycycline treatment (red) by Unweighted UniFrac distance. Significant differences were observed between MRMP patients without effective treatment and MRMP patients with doxycycline treatment. A PERMANOVA (α=0.05) with 999 random permutations, p = 0.001. Conclusion Respiratory dysbiosis was associated with persistent fever and disease severity in MRMP pneumonia. In our study, F. periodoticum negatively related to fever duration and disease severity. Compositional differences in the respiratory microbiome are associated with MRMP patients without effective treatment than MRMP patients who needed doxycycline treatment by LEfSE analysis LDA scores revealed differentially abundant bacteria in the respiratory microbiome of without effective treatment (blue) and doxycycline treatment (red) groups at genus level (A) and species level (B).The mean relative abundance of genera at right side. The mean relative abundance of genera at right side. (C) Receiver operating characteristic (ROC) curves of ASVs to predict MRMP patients without effective treatment or who needed doxycycline treatment. Pairwise Spearman rank correlation heat map of significantly different taxa in throat swabs at initial sampling and clinical severity score in MRMP patients without effective treatment/with doxycycline treatment The genus (A) and species (B) level. Genus and species were in rows; the correlation was indicated by color gradient. Disclosures All Authors: No reported disclosures.

Protective effect and mechanism of baicalin on lung inflammatory injury in BALB/cJ mice induced by PM2.5

The public health harms caused by fine particulate matter (PM2.5) have become a global focus, with PM2.5 exposure recognized as a critical risk factor for global morbidity and mortality. Chronic inflammation is the common pathophysiological feature of respiratory diseases induced by PM2.5 and is the most critical cause of all these diseases. However, presently there is a lack of effective preventive and therapeutic approaches for inflammatory lung injuries caused by PM2.5 exposure. Baicalin is a herb-derived effective flavonoid compound with multiple health benefits. This study established a murine lung inflammatory injury model via inhalation of PM2.5 aerosols. The data showed that after baicalin intervention, lung injury pathological score of baicalin (4.16 ± 0.54, 3.33 ± 0.76, 4.00 ± 0.45) and claricid (3.00 ± 0.78) treatments were markedly lower than PM2.5-treated mice (6.17 ± 0.31), and pathological damage was alleviated. Compared to the PM2.5 group, the spleen and lung indexes in the baicalin and claricid groups were significantly reduced. The inflammatory cytokines of TNF-α, IL-18, and IL-1β in serum, alveolar lavage fluid, and lung tissue were significantly decreased in the baicalin and claricid groups. The expressions of inflammatory pathway-related genes and proteins HMGB1, NLRP3, ASC, and caspase-1 were up-regulated in the PM2.5 group. The expressions of these genes and proteins were significantly decreased following baicalin treatment. The lung function indicators showed that the MV (65.94 ± 8.19 mL), sRaw (1.79 ± 0.08 cm H2O.s), and FRC (0.52 ± 0.01 mL) in the PM2.5 group were higher than in the control and baicalin groups, and respiratory function was improved by baicalin. PM2.5 exposure markedly altered the bacterial composition at the genus level. The dominant flora relative abundances of uncultured_bacterium_f_Muribaculaceae, Streptococcus, and Lactobacillus, were decreased from the control group (9.20%, 8.53%, 6.21%) to PM2.5 group (6.26%, 5.49%, 4.77%), respectively. Following baicalin intervention, the relative abundances were 9.72%, 6.65%, and 3.57%, respectively. Therefore, baicalin could potentially prevent and improve mice lung inflammatory injury induced by PM2.5 exposure. Baicalin might provide a protective role by balancing oropharyngeal microbiota and affecting the expression of the HMGB1/Caspase1 pathway.

The Past, Present, and Future of Kingella kingae Detection in Pediatric Osteoarthritis.

As a result of the increasing use of improved detection methods, Kingella kingae, a Gram-negative component of the pediatric oropharyngeal microbiota, is increasingly appreciated as the prime etiology of septic arthritis, osteomyelitis, and spondylodiscitis in children aged 6 to 48 months. The medical literature was reviewed to summarize the laboratory methods required for detecting the organism. Kingella kingae is notoriously fastidious, and seeding skeletal system samples onto solid culture media usually fails to isolate it. Inoculation of synovial fluid aspirates and bone exudates into blood culture vials enhances Kingella kingae recovery by diluting detrimental factors in the specimen. The detection of the species has been further improved by nucleic acid amplification tests, especially by using species-specific primers targeting Kingella kingae's rtxA, groEL, and mdh genes in a real-time PCR platform. Although novel metagenomic next-generation technology performed in the patient's plasma sample (liquid biopsy) has not yet reached its full potential, improvements in the sensitivity and specificity of the method will probably make this approach the primary means of diagnosing Kingella kingae infections in the future.

Limited Impact of SARS-CoV-2 on the Human Naso-Oropharyngeal Microbiota in Hospitalized Patients.

Numerous studies have reported dysbiosis in the naso- and/or oro-pharyngeal microbiota of COVID-19 patients compared with healthy individuals; however, only a few small-scale studies have also included a disease control group. In this study, we characterized and compared the bacterial communities of pooled nasopharyngeal and throat swabs from hospitalized COVID-19 patients (n = 76), hospitalized non-COVID-19 patients with respiratory symptoms or related illnesses (n = 69), and local community controls (n = 76) using 16S rRNA gene V3-V4 amplicon sequencing. None of the subjects received antimicrobial therapy within 2 weeks prior to sample collection. Both COVID-19 and non-COVID-19 hospitalized patients differed in the composition, alpha and beta diversity, and metabolic potential of the naso-oropharyngeal microbiota compared with local controls. However, the microbial communities in the two hospitalized patient groups did not differ significantly from each other. Differential abundance analysis revealed the enrichment of nine bacterial genera in the COVID-19 patients compared with local controls; however, six of them were also enriched in the non-COVID-19 patients. Bacterial genera uniquely enriched in the COVID-19 patients included Alloprevotella and Solobacterium. In contrast, Mogibacterium and Lactococcus were dramatically decreased in COVID-19 patients only. Association analysis revealed that Alloprevotella in COVID-19 patients was positively correlated with the level of the inflammation biomarker C-reactive protein. Our findings reveal a limited impact of SARS-CoV-2 on the naso-oropharyngeal microbiota in hospitalized patients and suggest that Alloprevotella and Solobacterium are more specific biomarkers for COVID-19 detection. IMPORTANCE Our results showed that while both COVID-19 and non-COVID-19 hospitalized patients differed in the composition, alpha and beta diversity, and metabolic potential of the naso-oropharyngeal microbiota compared with local controls, the microbial communities in the two hospitalized patient groups did not differ significantly from each other, indicating a limited impact of SARS-CoV-2 on the naso-oropharyngeal microbiota in hospitalized patients. Besides, we identified Alloprevotella and Solobacterium as bacterial genera uniquely enriched in COVID-19 patients, which may serve as more specific biomarkers for COVID-19 detection.

Air pollution from livestock farms and the oropharyngeal microbiome of COPD patients and controls.

Air pollution from livestock farms is known to affect respiratory health of patients with chronic obstructive pulmonary disease (COPD). The mechanisms behind this relationship, however, remain poorly understood. We hypothesise that air pollutants could influence respiratory health through modulation of the airway microbiome. Therefore, we studied associations between air pollution exposure and the oropharyngeal microbiota (OPM) composition of COPD patients and controls in a livestock-dense area. Oropharyngeal swabs were collected from 99 community-based (mostly mild) COPD cases and 184 controls (baseline), and after 6 and 12weeks. Participants were non-smokers or former smokers. Annual average livestock-related outdoor air pollution at the home address was predicted using dispersion modelling. OPM composition was analysed using 16S rRNA-based sequencing in all baseline samples and 6-week and 12-week repeated samples of 20 randomly selected subjects (n=323 samples). A random selection of negative control swabs, taken every sampling day, were also included in the downstream analysis. Both farm-emitted endotoxin and PM10 levels were associated with increased OPM richness in COPD patients (p<0.05) but not in controls. COPD case-control status was not associated with community structure, while correcting for known confounders (multivariate PERMANOVA p>0.05). However, members of the genus Streptococcus were more abundant in COPD patients (Benjamini-Hochberg adjusted p<0.01). Moderate correlation was found between ordinations of 20 subjects analysed at 0, 6, and 12weeks (Procrustes r=0.52 to 0.66; p<0.05; Principal coordinate analysis of Bray-Curtis dissimilarity), indicating that the OPM is relatively stable over a 12week period and that a single sample sufficiently represents the OPM. Air pollution from livestock farms is associated with OPM richness of COPD patients, suggesting that the OPM of COPD patients is susceptible to alterations induced by exposure to air pollutants.

Multi-omics association analysis reveals interactions between the oropharyngeal microbiome and the metabolome in pediatric patients with influenza A virus pneumonia.

Children are at high risk for influenza A virus (IAV) infections, which can develop into severe illnesses. However, little is known about interactions between the microbiome and respiratory tract metabolites and their impact on the development of IAV pneumonia in children. Using a combination of liquid chromatography tandem mass spectrometry (LC-MS/MS) and 16S rRNA gene sequencing, we analyzed the composition and metabolic profile of the oropharyngeal microbiota in 49 pediatric patients with IAV pneumonia and 42 age-matched healthy children. The results indicate that compared to healthy children, children with IAV pneumonia exhibited significant changes in the oropharyngeal macrobiotic structure (p = 0.001), and significantly lower microbial abundance and diversity (p < 0.05). These changes came with significant disturbances in the levels of oropharyngeal metabolites. Intergroup differences were observed in 204 metabolites mapped to 36 metabolic pathways. Significantly higher levels of sphingolipid (sphinganine and phytosphingosine) and propanoate (propionic acid and succinic acid) metabolism were observed in patients with IAV pneumonia than in healthy controls. Using Spearman's rank-correlation analysis, correlations between IAV pneumonia-associated discriminatory microbial genera and metabolites were evaluated. The results indicate significant correlations and consistency in variation trends between Streptococcus and three sphingolipid metabolites (phytosphingosine, sphinganine, and sphingosine). Besides these three sphingolipid metabolites, the sphinganine-to-sphingosine ratio and the joint analysis of the three metabolites indicated remarkable diagnostic efficacy in children with IAV pneumonia. This study confirmed significant changes in the characteristics and metabolic profile of the oropharyngeal microbiome in pediatric patients with IAV pneumonia, with high synergy between the two factors. Oropharyngeal sphingolipid metabolites may serve as potential diagnostic biomarkers of IAV pneumonia in children.

Composition of oropharyngeal microbiota in patients with COVID-19 of different pneumonia severity

To identify features of the taxonomic composition of the oropharyngeal microbiota of COVID-19 patients with different disease severity. The study group included 156 patients hospitalized with confirmed diagnosis of COVID-19 in the clinical medical center of Yevdokimov Moscow State University of Medicine and Dentistry between April and June 2021. There were 77 patients with mild pneumonia according to CT (CT1) and 79 patients with moderate to severe pneumonia (CT2 and CT3). Oropharyngeal swabs were taken when the patient was admitted to the hospital. Total DNA was isolated from the samples, then V3V4 regions of the 16s rRNA gene were amplified, followed by sequencing using Illumina HiSeq 2500 platform. DADA2 algorithm was used to obtain amplicon sequence variants (ASV). When comparing the microbial composition of the oropharynx of the patients with different forms of pneumonia, we have identified ASVs associated with the development of both mild and severe pneumonia outside hospital treatment. Based on the results obtained, ASVs associated with a lower degree of lung damage belong predominantly to the class of Gram-negative Firmicutes (Negativicutes), to various classes of Proteobacteria, as well as to the order Fusobacteria. In turn, ASVs associated with a greater degree of lung damage belong predominantly to Gram-positive classes of Firmicutes Bacilli and Clostridia. While being hospitalized, patients with severe pneumonia demonstrated negative disease dynamics during treatment significantly more often. We have observed differences in the taxonomic composition of the oropharyngeal microbiota in patients with different forms of pneumonia developed outside hospital treatment against COVID-19. Such differences might be due to the presumed barrier function of the oropharyngeal microbiota, which reduces the risk of virus titer increase.

541 Effect of therapeutic antibiotic exposure on oropharyngeal and fecal microbiota in infants with cystic fibrosis

541 Effect of therapeutic antibiotic exposure on oropharyngeal and fecal microbiota in infants with cystic fibrosis

The importance of the gut microbiota in the promotion, development, and treatment outcomes of cancer with special regard to the gut-respiratory axis.

The role of oral and pharyngeal microbiota is important in the promotion and development of head and neck cancers, as discussed in detail in this publication. The object of this work is to gather scientific information on the importance of the gut- respiratory axis in the promotion, development, and treatment outcome of head and neck cancer (HNSCC). Scientific knowledge about the interaction of head and neck cancer tumor cells and gut microbiota is residual, so examples of the relationship between the gut microbiota and the promotion of development in cases of other malignancies are also discussed. The subject of this work is also to present the importance of the gut-respiratory axis in promotion, development, and its impact on treatment outcomes of head and neck cancers.

A High-Risk Profile for Invasive Fungal Infections Is Associated with Altered Nasal Microbiota and Niche Determinants.

It is becoming increasingly clear that the communities of microorganisms that populate the surfaces exposed to the external environment, termed microbiota, are key players in the regulation of pathogen-host cross talk affecting the onset as well as the outcome of infectious diseases. We have performed a multicenter, prospective, observational study in which nasal and oropharyngeal swabs were collected for microbiota predicting the risk of invasive fungal infections (IFIs) in patients with hematological malignancies. Here, we demonstrate that the nasal and oropharyngeal microbiota are different, although similar characteristics differentiate high-risk from low-risk samples at both sites. Indeed, similar to previously published results on the oropharyngeal microbiota, high-risk samples in the nose were characterized by low diversity, a loss of beneficial bacteria, and an expansion of potentially pathogenic taxa, in the presence of reduced levels of tryptophan (Trp). At variance with oropharyngeal samples, however, low Trp levels were associated with defective host-derived kynurenine production, suggesting reduced tolerance mechanisms at the nasal mucosal surface. This was accompanied by reduced levels of the chemokine interleukin-8 (IL-8), likely associated with a reduced recruitment of neutrophils and impaired fungal clearance. Thus, the nasal and pharyngeal microbiomes of hematological patients provide complementary information that could improve predictive tools for the risk of IFI in hematological patients.

Assessment of Long-Term Macrolide Exposure on the Oropharyngeal Microbiome and Macrolide Resistance in Healthy Adults and Consequences for Onward Transmission of Resistance.

While the use of long-term macrolide therapy to prevent exacerbations in chronic respiratory diseases is widespread, its impact on the oropharyngeal microbiota and macrolide resistance, and the potential for onward transmission of resistance to close contacts are poorly understood. We determined the effects of long-term exposure to azithromycin or erythromycin on phenotypic and genotypic macrolide resistance within the oropharyngeal microbiome of healthy adults and their close contacts in a randomized, single-blinded, parallel-group trial of 4 weeks of twice-daily oral 400 mg erythromycin ethylsuccinate or twice-daily oral 125 mg azithromycin. Using oropharyngeal swabs collected from 20 index healthy adults and 20 paired close contacts, the oropharyngeal microbial composition and macrolide resistance in streptococci were assessed by 16S rRNA sequencing and antibiotic susceptibility testing of oropharyngeal cultures, respectively, at baseline and weeks 4 and 8 (washout). Targeted quantitative PCR of antibiotic resistance genes was performed to evaluate paired changes in resistance gene levels in index patients and close contacts and to relate the potential transmission of antibiotic resistance. Neither azithromycin nor erythromycin altered oropharyngeal microbiota characteristics significantly. Proportional macrolide resistance in oropharyngeal streptococci increased with both erythromycin and azithromycin, remaining above baseline levels for the azithromycin group at washout. Levels of resistance genes increased significantly with azithromycin[erm(B) and mef] and erythromycin (mef), returning to baseline levels at washout only for the erythromycin group. We found no evidence of onward transmission of resistance to close contacts, as indicated by the lack of concomitant changes in resistance gene levels detected in close contacts. (This study has been registered with the Australian and New Zealand Clinical Trials Registry under identifier ACTRN12617000278336.).

Characterization of Altered Oropharyngeal Microbiota in Hospitalized Patients With Mild SARS-CoV-2 Infection.

Coronavirus disease 2019 (COVID-19) remains a serious emerging global health problem, and little is known about the role of oropharynx commensal microbes in infection susceptibility and severity. Here, we present the oropharyngeal microbiota characteristics identified by full-length 16S rRNA gene sequencing through the NANOPORE platform of oropharynx swab specimens from 10 mild COVID-19 patients and 10 healthy controls. Our results revealed a distinct oropharyngeal microbiota composition in mild COVID-19 patients, characterized by enrichment of opportunistic pathogens such as Peptostreptococcus anaerobius and Pseudomonas stutzeri and depletion of Sphingomonas yabuuchiae, Agrobacterium sullae, and Pseudomonas veronii. Based on the relative abundance of the oropharyngeal microbiota at the species level, we built a microbial classifier to distinguish COVID-19 patients from healthy controls, in which P. veronii, Pseudomonas fragi, and S. yabuuchiae were identified as the most prominent signatures for their depletion in the COVID-19 group. Several members of the genus Campylobacter, especially Campylobacter fetus and Campylobacter rectus, which were highly enriched in COVID-19 patients with higher severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load and showed a significant correlation with disease status and several routine clinical blood indicators, indicate that several bacteria may transform into opportunistic pathogen in COVID-19 patients when facing the challenges of viral infection. We also found the diver taxa Streptococcus anginosus and Streptococcus alactolyticus in the network of disease patients, suggesting that these oropharynx microbiota alterations may impact COVID-19 severity by influencing the microbial association patterns. In conclusion, the low sample size of SARS-CoV-2 infection patients (n = 10) here makes these results tentative; however, we have provided the overall characterization that oropharyngeal microbiota alterations and microbial correlation patterns were associated with COVID-19 severity in Anhui Province.

Carriage and Transmission of Macrolide Resistance Genes in Patients With Chronic Respiratory Conditions and Their Close Contacts

Long-term macrolide therapy has been shown to provide benefit to those with a range of chronic respiratory conditions. However, concerns remain about the impact of macrolide exposure on the carriage and abundance of antibiotic resistance genes within the oropharynx. The potential for onward transmission of resistance from macrolide recipients to their close contacts also is poorly understood. Does long-term macrolide use impact carriage of resistance within the oropharyngeal microbiota in people with chronic respiratory conditions and risk of onward transmission to their close contacts? Oropharyngeal swabs were collected from 93 individuals with chronic respiratory conditions, 53 of whom were receiving long-term macrolide therapy. An oropharyngeal swab also was collected from a close cohabiting contact of each patient. Detection and abundance of 10 macrolide-associated resistance genes with the potential to disseminate via horizontal gene transfer were assessed by quantitative polymerase chain reaction analysis. Detection of resistance genes in macrolide recipients was comparable with that in nonrecipients. However, the normalized gene abundance of erm(B) was significantly higher in the macrolide recipient group (P= .045). Among the close contacts, no between-group differences in resistance gene detection or abundance were identified. Within-group analysis showed that the detection of erm(F) and mef in macrolide recipients, but not nonrecipients, was associated significantly with detection in close contacts (P= .003 and P= .004, respectively). However, between-group analysis showed that treatment group did not predict cocarriage between patients and their close contacts (P > .05 for each gene). Although levels of erm(B) were higher in those receiving long-term macrolide therapy and evidence of gene cocarriage with close contacts was found, no evidence was found that macrolide use increased the onward transmission risk to their close contacts. This study therefore addresses concerns that long-term macrolide therapy could promote the dissemination of transmissible macrolide resistance.

Особливості мікробіоти ротоглотки дітей, хворих на бронхіальну астму та гостру респіраторну інфекцію

Стаття присвячена порівнянню складу колонізуючої мікрофлори ротоглотки дітей, які хворіють на бронхіальну астму (БА) та гостру респіраторну інфекцію (ГРІ). Константними для біотопів ротоглотки дітей з ГРІ та БА були стафілококи та α-гемолітичні стрептококи. Групи дослідження відрізнялися за складом другорядних за значенням мікроорганізмів: при ГРІ виділені Streptococcus spp. з β-гемолізом, E.coli та Candida spp., при БА — представники автохтонної мікрофлори (Streptococcus spp. з β-гемолізом, Moraxella spp., Corynebacterium spp.). Варіабельність видового складу біоти ротоглотки у хворих на ГРІ майже вдвічі перевищувала таку в пацієнтів із БА. Домінуючими за показником зустрічальності Рі мікроорганізмами при обох захворюваннях були стафіло- та стрептококи.

The Impact of Mouthwash on the Oropharyngeal Microbiota of Men Who Have Sex with Men: a Substudy of the OMEGA Trial.

ABSTRACTMouthwash is a commonly used product and has been proposed as an alternative intervention to prevent gonorrhea transmission. However, the long-term effects of mouthwash on the oral microbiota are largely unknown. We investigated the impact of 12 weeks of daily mouthwash use on the oropharyngeal microbiota in a subset of men who have sex with men who participated in a randomized trial comparing the efficacy of two alcohol-free mouthwashes for the prevention of gonorrhea. We characterized the oropharyngeal microbiota using 16S rRNA gene sequencing of tonsillar fossae samples collected before and after 12 weeks of daily use of Listerine mouthwash or Biotène dry mouth oral rinse. Permutational multivariate analysis of variance (PERMANOVA) was used to assess differences in oropharyngeal microbiota composition following mouthwash use. Differential abundance testing was performed using ALDEx2, with false-discovery rate correction. A total of 306 samples from 153 men were analyzed (Listerine, n = 78 and Biotène, n = 75). There was no difference in the overall structure of the oropharyngeal microbiota following Listerine or Biotène use (PERMANOVA P = 0.413 and P = 0.331, respectively). Although no bacterial taxa were significantly differentially abundant following Listerine use, we observed a small but significant decrease in the abundance of both Streptococcus and Leptotrichia following Biotène use. Overall, our findings suggest that daily use of antiseptic mouthwash has minimal long-term effects on the composition of the oropharyngeal microbiota.IMPORTANCE Given the role of the oral microbiota in human health, it is important to understand if and how external factors influence its composition. Mouthwash use is common in some populations, and the use of antiseptic mouthwash has been proposed as an alternative intervention to prevent gonorrhea transmission. However, the long-term effect of mouthwash use on the oral microbiota composition is largely unknown. We found that daily use of two different commercially available mouthwashes had limited long-term effects on the composition of the oropharyngeal microbiota over a 12-week period. The results from our study and prior studies highlight that different mouthwashes may differentially affect the oral microbiome composition and that further studies are needed to determine if mouthwash use induces short-term changes to the oral microbiota that may have detrimental effects.

Боль в горле. Перекрестье проблем и поиски решений

The article presents a brief review of the current issues relating to the treatment of acute infectious inflammatory diseases associated with sore throat. Painful throat is one of the most common reasons for the administration of systemic antibacterial drugs as a baseline therapy which, in turn, may facilitate a rise in antibiotic resistance. Recently the focus has shifted to the antibacterial therapy impact on the qualitative and quantitative composition of the microbiota. The review elucidates the opportunities of successful etiotropic therapy amid a low risk of the antibiotic resistance development and a lack of the adverse effects on the oropharyngeal microbiota. Updated information is provided characterizing the pharmacological activity of a bacterium-produced non-ribosomal antimicrobial peptide Gramicidin S and Cetylpyridinium chloride, an antiseptic agent. The highest potency of topical medications can be achieved due to the combined action of multiple synergistic components. A potential combined use of Gramicidin S and Cetylpyridinium chloride is discussed in the review from the standpoint of the risk of antibiotic resistance and the impact on microbiota. The authors conclude that for the treatment of infectious inflammatory diseases of the upper respiratory tract associated with sore throat it is advisable to select biocenosis-saving topical etiotropic therapy. KEYWORDS: Gramicidin S, non-ribosomal antimicrobial peptides, Cetylpyridinium chloride, topical etiotropic therapy, bactericidal activity, antibiotic resistance, microbiocenosis-saving therapy, pharyngitis, tonsillopharyngitis. FOR CITATION: Radtsig E.Yu., Gurov A.V. Sore throat. Crossing problems and finding solutions. Russian Journal of Woman and Child Health. 2022;5(3):228–236 (in Russ.). DOI: 10.32364/2618-8430-2022-5-3-228-236.

Correction of the oropharyngeal and gut microbiota in children by plant extracts containing natural products

The widespread use of antibacterial drugs for the treatment of respiratory diseases causes antimicrobial resistance in opportunistic microorganisms, which leads to the chronic forms of respiratory diseases and contributes to the risk of repeated respiratory infections. One of the new therapeutic solutions is the use of multicomponent water-soluble plant extracts. The goal of this study was to evaluate the antibacterial efficacy of the extracts of multicomponent herbal remedies versus the synthetic antiseptic for the treatment of the oropharyngeal and gut opportunistic microflora in children with chronic tonsillitis. In a retrospective study, we compared the effectiveness of the plant extract Tonzinal (experimental group, 100 patients) versus the Miramistin antiseptic agent (control group, 40 patients) for the treatment of chronic tonsillitis in children 5 to 15 years old using various treatment regimens. The oropharyngeal microbiocenosis was investigated by the bacteriological analysis of smears from the posterior wall of the pharynx and tonsils. Bacterial strains were isolated by inoculation on liquid agar media with the subsequent identification of Staphylococcus aureus, Streptococcus pyogenes, Candida spp., Moraxela cataralis, and Mycoplasma pneumonie according to the morphological and biochemical characteristics. For the bacteriological analysis of gut microbiocenosis, Staphylococcus aureus, Streptococcus spp., Candida spp., Klebsiella spp., Clostridiums spp., and Proteus spp. were isolated from the fecal filtrate and then identified by the same methods. The occurrence rate of microorganisms in patients of the experimental and control groups was compared before and after the 10-day course of therapy. A statistically significant decrease in the occurrence rate of Staphylococcus aureus (from 25% to 0%, p&lt;0.01) and Candida spp. (from 18% to 0%, p&lt;0.01) in the oropharynx of patients in the experimental group and from 20% to 7.5% and from 5% to 0% (p&lt;0.05), respectively, in the control group was observed. A statistically significant decrease in the occurrence rate of Streptococcus pyogenes was only observed in the experimental group (from 30% to 0%, p&lt;0.01). Treatment with Tonzinal or Miramistin did not lead to the statistically significant changes in the occurrence rate of opportunistic microorganisms in the gut microflora of the patients in both groups. Therefore, we have shown a higher antimicrobial efficacy of Tonzinal versus the Miramistin antiseptic for the treatment of the oropharyngeal opportunistic microorganisms in children with chronic tonsillitis.

Oropharyngeal microbiota profi ling in chronic tonsillitis patients receiving polyvalent pyobacteriophage: A non-randomised experimental clinical trial

Background . Recent years have witnessed a 1.5–1.8-fold growth of chronic palatine tonsillitis. Choosing optimal treatment remains relevant in this illness despite ample research and improvement in therapy and diagnosis. Objectives . An analysis of oropharyngeal microflora in chronic tonsillitis patients receiving a polyvalent pyobacteriophage treatment. Methods . A total of 126 patients diagnosed with compensated chronic tonsillitis were followed up over 2018–2021. Qualitative and quantitative traits of oropharyngeal microflora have been assessed at baseline, immediately upon completion and past 3 months of treatment. The patients were separated between two cohorts: the main one ( n = 65) had palatine tonsil lacunae irrigation with a Tonsillor MM unit and received polyvalent pyobacteriophage, while the comparison cohort ( n = 61) only had palatine tonsil lacunae sanitation with Tonsillor MM. The trial included a control healthy volunteers cohort. Pearson’s chi-square method was used for statistical analyses with the SPSS 23 software. Statistical significance was obtained at p &lt; 0.05. Results. Quantitative comparisons of microbiotic strain persistence in tonsillar mucosa (isolation rate, microbial colonisation density) showed a significant prevalence of enterobacterial staphylococci and ß-haemolytic streptococci, Gram-negative anaerobic bacteria and fungi in chronic tonsillitis patients compared to the control cohort ( p &lt; 0.05). Therapy positively impacted microbiota vs. control, but the best effect was observed with polyvalent pyobacteriophage. Microbiological assays in dynamic patient follow-up demonstrated stability of the results attained. The Tonsillor MM sanitation cohort revealed a 2–3 degree dysbiosis in 47.5% (29) patients in 3 months, while the polyvalent pyobacteriophage cohort only had 7.7% (5) such patients ( p &lt; 0.01). Conclusion. The trial demonstrates efficacy and relevance of pyobacteriophage treatment in chronic tonsillitis, primarily at the microenvironmental level.

OROPHARYNGEAL MICROBIOTA IN CHILDREN WITH WEB INFECTION ON THE BACKGROUND OF ANTIBIOTIC THERAPY

According to statistics from the World Health Organization, infectious mononucleosis caused by Epstein-Barr virus affects 90% of the world's population. The aim of this study was to study the composition of the oropharyngeal microbiota and to determine the antibiotic sensitivity of its representatives, which are released in clinically significant concentrations from children with WEB infection who received antibiotic therapy. 28 patients with WEB infection in children aged 5 to 16 years were examined. Among the 28 children in inpatient treatment, 78.6% were patients under the age of 10. All children received antibiotic therapy, although according to treatment protocols, it is indicated only in the case of a bacterial infection.&#x0D; Streptococcus spp. with β-hemolysis (64.3%). Detection of S. aureus in 35.7% of patients indicates a violation of the structure of the normal microbiocenosis of the oropharynx. The study of antibiotic susceptibility of staphylococci and streptococci showed the presence of resistance in 52.6% of isolated strains of streptococci and 25.0% of staphylococci to azithromycin.

Мікробіота ротоглотки в дітей у періоді висипання кору

Метою нашої роботи було вивчити мікробіоту ротоглотки у хворих на кір дітей. Матеріали та методи. Нами проведено спостереження за 35 дітьми, які захворіли на типову форму кору та знаходились на стаціонарному лікуванні. Серед обстежених 23 (65,7 %) мали неускладнений перебіг, у 12 (34,3 %) пацієнтів кір ускладнився пневмонією, бронхітом чи отитом. Матеріал з ротоглотки в періоді висипань досліджено мікробіологічним методом. Уточнюючу ідентифікацію проводили за допомогою напівавтоматичного мікробіологічного аналізатора Vitek-2. Для оцінки частоти зустрічальності у популяції різних мікроорганізмів на слизовій ротоглотки використовували показник зустрічальності (Рі), про ступінь домінування того чи іншого представника мікробіоти в угрупованні судили за частотою його появи у зразках, використовуючи при цьому індекс постійності (С, %). Статистична обробка даних проводилась за допомогою пакета стандартних програм для персонального комп’ютера. Результати. Дослідження мікробіоти ротоглотки у спостережуваних дітей, які хворіли на кір, виявили домінування облігатно резидентних мікроорганізмів: α- та β-гемолітичні стрептококи, Lactobacillus spp., Neisseria spp. Представниками транзиторної мікробіоти були Enterobacter spp., Pseudomonas spp. і Micrococcus spp. Факультативно резидентну флору ротоглотки становили мікроорганізми: Staphylococcus spp., зокрема S.aureus, Streptococcus spp. і з γ-гемолізом, Corynebacterium spp., Moraxella spp., Candida spp. та E.coli і Enteroccocus spp. Максимальний показник зустрічальності мікроорганізмів у ротоглотці хворих на кір був притаманний стрептококам, α- та β-гемолітичні стрептококи виявлялись з однаковою частотою. Висновки. Таким чином, у дітей, хворих на кір, є порушення нормоценозу ротоглотки, що проявляються зменшенням С та Рі константних штамів Staphylococcus spp., Neisseria spp. та Lactobacillus spp. Збільшення індексу постійності та показника зустрічальності свідчить про порушення нормоценозу на межі з дисбактеріозом ротоглотки у дітей, хворих на кір. Порушення співвідношення α-, γ- та β-гемолітичних стрептококів у бік зростання останніх в поєднанні з вираженими факторами їх патогенності є ймовірною причиною бактеріальних ускладнень стрептококової етіології.